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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-12-16
pubmed:abstractText
Interleukin (IL)-12 is a key factor for inducing cellular immune responses, which play a central role in the eradication of cancer. In the present study, in order to create a dendritic cell (DC)-based vaccine capable of positively skewing immune response toward a cellular immunity-dominant state, we analyzed immunological characteristics and vaccine efficacy of DCs cotransduced with melanoma-associated antigen (gp100) and IL-12 gene (gp100+IL12/DCs) by using RGD fiber-mutant adenovirus vector (AdRGD), which enables highly efficient gene transduction into DCs. gp100+IL12/DCs could simultaneously express cytoplasmic gp100 and secretory IL-12 at levels comparable to DCs transduced with each gene alone. In comparison with DCs transduced with gp100 alone (gp100/DCs), upregulation of major histocompatibility complex class I, CD40, and CD86 molecules on the cell surface and more potent T-cell-stimulating ability for proliferation and interferon-gamma secretion were observed as characteristic changes in gp100+IL12/DCs. In addition, administration of gp100+IL12/DCs, which were prepared by a relatively low dose of AdRGD-IL12, could induce more potent tumor-specific cellular immunity in the murine B16BL6 melanoma model than vaccination with gp100/DCs. However, antitumor effect and B16BL6-specific cytotoxic T-lymphocyte activity in mice vaccinated with gp100+IL12/DCs diminished with increasing AdRGD-IL12 dose during gene transduction, and paralleled the decrease in presentation levels via MHC class I molecules for antigen transduced with another AdRGD. Collectively, our results suggested that optimization of combined vector dose was required for development of a more efficacious DC-based vaccine for cancer immunotherapy, which relied on genetic engineering to simultaneously express tumor-associated antigen and IL-12.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0929-1903
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
72-83
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:15389286-Adenoviridae, pubmed-meshheading:15389286-Animals, pubmed-meshheading:15389286-Antigens, Neoplasm, pubmed-meshheading:15389286-Antigens, Surface, pubmed-meshheading:15389286-Cancer Vaccines, pubmed-meshheading:15389286-Dendritic Cells, pubmed-meshheading:15389286-Female, pubmed-meshheading:15389286-Genetic Engineering, pubmed-meshheading:15389286-Interleukin-12, pubmed-meshheading:15389286-Melanoma, pubmed-meshheading:15389286-Melanoma-Specific Antigens, pubmed-meshheading:15389286-Mice, pubmed-meshheading:15389286-Mice, Inbred C57BL, pubmed-meshheading:15389286-Neoplasm Proteins, pubmed-meshheading:15389286-T-Lymphocytes, Cytotoxic, pubmed-meshheading:15389286-Transduction, Genetic, pubmed-meshheading:15389286-Tumor Cells, Cultured, pubmed-meshheading:15389286-Up-Regulation
pubmed:year
2005
pubmed:articleTitle
Immunological properties and vaccine efficacy of murine dendritic cells simultaneously expressing melanoma-associated antigen and interleukin-12.
pubmed:affiliation
Department of Biopharmaceutics, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan. okada@mb.kyoto-phu.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't